Wilms tumor is the most frequent
renal neoplasm in children, but our understanding of its genetic basis is still limited. We performed
cDNA microarray experiments using 63 primary Wilms
tumors with the aim of detecting new candidate genes associated with
malignancy grade and
tumor progression. All
tumors had received preoperative
chemotherapy as mandated by the
SIOP protocol, which sets this study apart from related approaches in the Unites States that are based on untreated samples. The stratification of expression data according to clinical criteria allowed a rather clear distinction between different subsets of Wilms
tumors. Clear-cut differences in expression patterns were discovered between relapse-free as opposed to relapsed
tumors and
tumors with intermediate risk as opposed to high risk histology. Several differentially expressed genes, e.g.TRIM22, CENPF, MYCN, CTGF, RARRES3 and EZH2, were associated with
Wilms tumor progression. For a subset of differentially expressed genes, microarray data were confirmed by real-time RT-PCR on the original set of
tumors. Interestingly, we found the
retinoic acid pathway to be deregulated at different levels in advanced
tumors suggesting that treatment of these
tumors with
retinoic acid may represent a promising novel therapeutic approach.